Keywords

Nitric OxideLiver FibrosisKupffer CellEicosanoidStellate Cell

Introduction

Among the hormone class of the eicosanoids, PGE2 plays a predominant role in liver (patho) physiology. Liver-specific responses, like regulation of blood glucose homeostasis, sinusoidal blood flow within the liver, properties of the transendothelial barrier within the liver, synthesis and release of important other mediators like cytokines, growth factors or nitric oxide, and liver fibrogenesis have been shown to be mediated or regulated by PGE2 [1]. Within the liver, the main producers of PGE2 are the Kupffer cells. The synthesis of PGE2 in Kupffer cells is controlled at multiple levels. The action of PGE2 on its target cells is mediated by 4 classes of PGE2 receptors (EP1, EP2, EP3, EP4). Each of these receptors converts the information of PGE2 by different intracellular signal pathways to a specific cellular response [2].

Besides eicosanoids, LPS induces in Kupffer cells the release of other mediators, including IL-1, IL-10, TNF-alpha, ET-1, and NO (1). The release of IL-1, TNF-alpha and ET-1 is totally suppressed by PGE2, the release of IL-10 and NO (1) is enhanced by PGE2 (Fig. 3). The regulation of the synthesis of IL-1, IL-10, TNF-alpha (Fig. 4) and ET-1 in Kupffer cells by PGE2 is mediated by EP-2 and EP-4, as demonstrated by the use of PGE2-receptor-specific agonists (EP-1/-2/-3/-4:ONO-DI-004/-AE1-259/-AE-248/-AE1-329).

Figure 3

Effect of PGE2 on LPS-induced formation of TNF-alpha, IL-1, ET-1, IL-10 and NO.

Copyright

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.